Tetrahydrobiopterin Improves Impaired Endothelium-Dependent Forearm Vasodilation in Patients with Heart Failure

Abstract

Endothelium-dependent vasodilation is impaired in patients with chronic heart failure (CHF). However, the mechanisms responsible for this effect are not fully understood. The vasodilator response to acetylcholine (ACh) has been used to examine the endothelium-dependent vasodilation in humans and is known to be mediated by nitric oxide (NO). The impaired production of NO or an increase in its degradation is thought to be responsible for the endothelial dysfunction in CHF. The aim of this study was to determine whether the decrease in availability of tetrahydrobiopterin (BH(4)), an essential cofactor of NO synthase, contributes to the impairment of endothelium-dependent vasodilation in patients with CHF. Fourteen patients with CHF (New York Heart Association functional class II-IV, age: 59 +/- 4 years, ejection fraction: 28 +/- 3%) and seven age-matched control subjects were examined. Forearm blood flow (FBF) was measured by plethysmography during an intra-arterial infusion of a graded dose of ACh (4, 8, and 16 microg/min) and sodium nitroprusside (SNP) (0.8, 1.6, and 3.2 microg/min). These procedures were repeated during a co-infusion of BH(4) (400 microg/min). The forearm vasodilator response to ACh was significantly enhanced during co-infusion of BH(4) in patients with CHF, whereas no effect was observed in healthy subjects. In contrast, the response to SNP was not affected by BH(4) in either group. The administration of BH(4) did not alter the baseline FBF in either group. These results suggest that an acute administration of BH(4 ) improves endothelium-dependent forearm vasodilation in patients with CHF.